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Science finds out how type 1 diabetes holds back the repair process in cells

by Barbara Hewitt on August 6, 2015

Scientists say they have found an advanced understanding of how the cellular repair process is impaired in type 1 diabetes, which can cause cell death and lead to complications.

The new understanding could lead to therapies that detect complications involving the kidneys, eyes, nerves and heart at an early stage and therefore lead to healthier and more productive lives for people with type 1 diabetes.

stem-cell“Even with very good glycaemic control people with type 1 diabetes can still develop complications that impact their ability to work and quality of life,” said the senior author of the new study, Rohit Kulkarni of Joslin Diabetes Centre and associate professor of medicine at Harvard Medical School.

Until now working out exactly how the body’s cellular repair process malfunctions in type 1 diabetes has been challenging because of a lack of animal and cellular models that can precisely replicate the human disease for scientific investigation.

This new study approached this problem by inducing pluripotent stem (iPS) cells, which have the potential to differentiate into any type of cell in the body, to model the disease. They were derived from skin cells obtained from patients who have had type 1 diabetes for 50 years or more and also from healthy controls.

“Studying iPS cells that come directly from patients with the disease offers a major advantage over other models,” explained Dr. Kulkarni.

Participants were classified according to the severity of complications with Medalist +C for severe complications and Medalist -C for absent or mild complications.

Genetic analysis of the iPS and skin cells showed remarkable differences in expression of genes and proteins in the Medalist +C group compared to the Medalist -C group and the controls.

Kulkarni explained that in the Medalist +C group there were alterations in the DNA damage checkpoint pathway machinery that monitors the DNA repair process of the body’s cells. This machinery functioned well in the Medalist -C group, ensuring that damaged cells were repaired, preventing cell death and the development of complications.

Further evidence was provided by nerve cells that were differentiated from the iPS cells: nerve cells from the Medalist +C group were more prone to early death than nerve cells from the Medalist -C group.

The analysis revealed higher levels of a protein known as miR200 in the Medalist +C group than in the Medalist -C group and controls. “This is a very significant finding because miR200 plays an important role in the DNA repair process,” said Kulkarni.

When the scientists reduced expression of miR200 in iPS and skin cells from the Medalist +C group, the DNA damage checkpoint pathway machinery was restored and DNA damage was reduced in the cells.

Kulkarni pointed out that this makes miR200 a promising potential target for therapeutic interventions and also a possible biomarker for early detection of the development of complications.

“We need to figure out the exact mechanisms by which miR200 regulates the DNA repair process and also determine if miR200 can be detected in the bloodstream and serve as an effective biomarker for complications,” Kulkarni added.

The scientists now plan to use the iPS cells to differentiate into kidney, eye and vascular cells and learn more about how complications develop in those cells. It is hoped that these differentiated cells could provide a faster and more efficient way to test which medications are most effective in different patients.

The opinions expressed in this article do not necessarily reflect the views of the Community and should not be interpreted as medical advice. Please see your doctor before making any changes to your diabetes management plan.

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